Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
;
(6): 898-906, 2020.
Artigo
em Inglês
| WPRIM
| ID: wpr-881035
ABSTRACT
Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Ácido Tauroquenodesoxicólico
/
Transdução de Sinais
/
Linhagem Celular
/
Citocinas
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Proteínas Quinases Dependentes de AMP Cíclico
/
AMP Cíclico
/
Receptores Acoplados a Proteínas G
/
Inflamação
/
Macrófagos
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Chinese Journal of Natural Medicines (English Ed.)
Ano de publicação:
2020
Tipo de documento:
Artigo
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